Inflammation is a key defense mechanism of the body that is activated as a result of tissue injury. The inflammatory process is self-containing, however, under certain pathophysiological conditions the inflammatory process tends to perpetuate itself, giving rise to chronic inflammatory diseases like bronchial asthma, rheumatoid arthritis, etc.
Although the exact cellular and molecular bases of most chronic inflammatory disease remain unclear, it has become apparent that several inflammatory cells act in concert towards initiation and perpetuation of an inflammatory response by releasing a wide range of chemokine, cytokine, proteolytic enzymes and other bioactive molecules. Mast cells primed by lymphocytes interact with environmental allergens and release mediators like histamine, prostaglandin, leukotrienes etc. (Clin. Exp. Allergy 32:1682, 2002) to initiate an early inflammatory response. This is followed by a delayed inflammatory response due to release of cytokines (IL-4, IL-5, IL-6, IL-8, IL-13, GM-CSF and TNF-alpha), chemokines and proteolytic enzymes (chymase, tryptase) (Chest 112:523, 1997; Lancet 350:59, 1997) that not only bring about tissue damage, but attract other inflammatory cells and initiate tissue fibrosis, and the cycle continues. Eosinophils infiltrate inflamed tissue following allergen-mast cell interaction in bronchial asthma and allergic rhinitis. Evidence is emerging that mast cells also interact with bacterial endotoxins leading to generation of cytokines like TNF-alpha, that encourage neutrophil influx into the site of inflammation (Br. J. Pharmacol., 123:31, (1998); Br. J. Pharmacol., 128:700,(1999); Br. J. Pharmacol., 136:111,(2002); J. Clin. Invest., 109:1351,(2002)). Involvement of mast cells in the inflammatory response of chronic obstructive pulmonary disease (New Eng. J. Med., 347:1040,(2002); Thorax, 57:649,(2002)), inflammatory bowel disease (Gut., 45,Suppl. II6,(1999)) as well as in rheumatoid arthritis (Science, 297:1626,(2002)), pathologies with prominent neutrophilic inflammation, has been proposed.
U.S. Pat. No. 6,329,344 B1 discloses several monosaccharide derivatives said to be useful as cell adhesion inhibitors. It generally relates to substituted pentose and hexose monosaccharide derivatives, which are said to exhibit cell adhesion inhibitory and anti-inflammatory activities. U.S. Pat. No. 6,590,085 B1 discloses several monosaccharide derivatives described as inhibitors of cell adhesion and cell adhesion mediated pathologies, including inflammatory and autoimmune diseases. U.S. Patent Application 2002/0173632 A1 discloses furanose and amino furanose compounds reportedly useful for rheumatoid arthritis, immunomodulatory diseases inflammatory and proliferative diseases. U.S. Pat. No. 5,298,494 discloses derivatives of monosaccharides, which are said to exhibit anti-proliferative and/or anti-inflammatory activity and are useful for treating mammals having inflammatory disorders and/or autoimmune disorders. U.S. Pat. No. 4,996,195 discloses derivatives of α-D-glucofuranose and α-D-allofuranose described as useful for treating animals and mammals with inflammatory and/or autoimmune disorders.
WO 93/13117 and U.S. Pat. No. 5,360,792 discloses 5- or 6-deoxy hexose monosaccharides having a saturated nitrogen containing heterocycle described as useful as anti-proliferative and anti-inflammatory compounds. WO 94/28910 discloses 5,6-dideoxy-5-amino derivatives of idose and 6-deoxy-6-amino derivatives of glucose, which reportedly exhibit immunomodulatory, anti-inflammatory and anti-proliferative activity. WO 94/11381 discloses derivatives of pentose monosaccharides described as useful as anti-proliferative and anti-inflammatory compounds. U.S. Pat. No. 5,010,058 discloses 3,5,6-disubstituted derivatives of 1,2-O-isopropylidene-α-O-glucofuranoside described as useful for treating inflammatory and autoimmune disorders. U.S. Pat. No. 4,849,512 discloses 3-acylamino-3-deoxyallose derivatives. U.S. Pat. No. 5,367,062 discloses disubstituted and deoxy disubstituted derivatives of α-D-lyxofuranosides reportedly having anti-inflammatory and anti-proliferative activity. U.S. Pat. No. 5,360,794 discloses disubstituted derivatives of α-D-mannofuranoside reportedly having anti-inflammatory and anti proliferative activity. WO 03/029263 discloses 3-deoxy-3-amide derivatives of carbohydrates described as useful as inducers of erythroid cell differentiation. French Patent 2735130 discloses regiospecific synthesis of carbamic polyesters.